FDA Approves First HPV Test for Primary Cervical Cancer Screening

Alberto Gutierrez, PhD

The FDA has approved the cobas HPV Test as a first-line screening tool for cervical cancer in women 25 and older, making it the first-ever approved alternative to Pap smear.

The approval was based on results from the large ATHENA study, which demonstrated that the cobas HPV test was 15.63% more sensitive at detecting cervical intraepithelial neoplasia grade 3 (CIN3) when compared with liquid-based cytology. The FDA initially approved the cobas HPV test in 2011 as a secondary or adjunctive cervical screening tool. The test, which is a qualitative multiplex assay manufactured by Roche Diagnostics, detects genotype-specific information from 14 high-risk HPV types, including HPV 16 and 18.

“Today’s approval offers women and physicians a new option for cervical cancer screening,” Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, said in a statement. “Roche Diagnostics conducted a well-designed study that provided the FDA with a reasonable assurance of the safety and effectiveness when used as a primary screening tool for cervical cancer.”

In response to the FDA's decision, the Society of Gynecologic Oncology (SGO) announced that it was developing interim guidance documents to help determine how to best incorporate first-line HPV testing. In the same statement, SGO noted that primary HPV testing was not likely to replace Pap smear.

"We are committed to working with the medical community and professional organizations to put the necessary clinical practice guidelines in place to encourage providers to incorporate this new screening strategy alternative in their patient protocols,” Roland Diggelmann, the Chief Operating Officer of the Diagnostics Division at Roche, said in a release. "We are very pleased that the FDA has approved this test for first-line use in cervical cancer screening.”

In the ATHENA trial, liquid-based cytology or HPV DNA testing was used to analyze specimens from 41,955 women aged 25 or older. Women with atypical squamous cells of undetermined significance or those with worse cytology underwent colposcopy and diagnostic biopsies. The primary endpoint of the study was histologically confirmed ≥CIN3.

In materials compiled for the advisory panel, the FDA developed a comparison between the cobas HPV Test and cytology alone based on their assessment of the data from the ATHENA trial. In this analysis, the sensitivity for ≥CIN3 was 58.26% (95% CI, 44.02-74.37) for the cobas HPV Test compared with 42.63% (95% CI, 31.75-55.41) for cytology alone.

The positive predictive value for the risk of ≥CIN3 in women referred to colposcopy by the cobas HPV Test was 12.25% (95% CI, 10.69-13.91) compared with 6.47% (95% CI, 5.54-7.50) for cytology alone. The FDA established that the false positive rate for ≥CIN3 was 4.09% (95% CI, 3.89-4.28) for the cobas HPV Test compared with 6.04% (95% CI, 5.81-6.27) for cytology alone.

The approval followed a unanimous 13-0 vote from the FDA’s Microbiology Devices Panel supporting the claim that the benefits of the test outweighed its risk and that the test was safe and effective.

"Using the cobas HPV Test as a primary screen means that women will have the opportunity to receive a better and more accurate standard of care," Mark H. Stoler, MD, professor emeritus of Pathology and Clinical Gynecology at the University of Virginia Health System, said in a release. "Clinically validated HPV screening detects the virus that causes cervical cancer and does a better job identifying women at risk than Pap testing alone. But most importantly, women found to be HPV-negative are provided a greater sense of security that they are safe from the disease."

Updated Friday April 25, 2014, to reflect the SGO guideline statement.